1. Field of the Invention
The invention relates to the use of hemoglobin solutions to treat patients in need of blood or other oxygen carrier. More specifically, the invention relates to the administration of a hemoglobin solution to patients suffering from massive blood loss.
2. Description of the Related Art
The following description refers to a number of references by numeral in parentheses. Complete citations to the references may be found in the section entitled “References” immediately preceding the claims.
The critical issues in resuscitation from acute blood loss in trauma and surgery are restoration of total blood volume and maintenance of sufficient oxygen-carrying capacity to avoid inadequate delivery of oxygen to tissues. (1, 2, 3, 4) Inadequate volume replacement leads to a fall in blood pressure and eventual hypovolemic shock. Insufficient red cell replacement may lead to critical levels of anemia, irreversible ischemia, and death. (5, 6)
The physiologic consequences of profound anemia are well understood. In a bleeding but otherwise healthy surgical patient, cardiovascular compensation should be adequate until red blood cell (RBC) hemoglobin concentration falls below of 5 g/dL. (26) As blood loss continues and the RBC hemoglobin concentration falls further, the compensatory responses begin to fail. (7, 8, 29, 31) Cardiac compensation becomes inadequate when RBC hemoglobin concentration falls below 3.5 g/dL, (32, 33, 34, 35) with reported mortality rates ranging from 50-95% when the RBC hemoglobin concentration falls below 3 g/dL. (9, 10, 11, 12, 13, 14, 29)
Current resuscitation methods involve initial asanguineous (non-blood) volume replacement with salt solutions, followed by red cell transfusions when compatible blood is available and adequate in supply. (1, 2) The goal of current treatment methods is to restore sufficient blood volume to maintain a mean arterial pressure above 60 mmHg, and to replace sufficient red cells to maintain a circulating hemoglobin level above 6 g/dL according to the American Society of Anesthesiologists (ASA), (7) or between 7-10 g/dL according to the National Institutes of Health (NIH) Consensus Conference. (8) However, there are occasions when red cells are temporarily unavailable, inadequate in supply, or cannot be used due to incompatibility or religious objection. This may lead to urgent, life-threatening situations, with reported mortality rates of 50-95% for hemoglobin levels ≦3 g/dL. (9, 10, 1, 12, 13, 14) What is needed in these situations is a substitute for whole blood such as a solution for restoring volume as well as oxygen carrying capacity. Moreover, considering the risks of infection or other toxicity associated with blood replacement therapy, patients may choose an oxygen carrier solution to restore volume and oxygen carrying capacity, even when whole blood is available.
Prior to the present invention, the benefits of using a polymerized hemoglobin solution as a treatment for massively bleeding patients had not been studied. While U.S. Pat. No. 6,498,141 teaches that up to 5 L of a hemoglobin solution may be administered to a patient, there has been no suggestion of the use of a polymerized hemoglobin solution to treat patients suffering from massive hemorrhage, including those patients having total Hb less than 7 g/dL. It had been reported that nearly all patients with Hb level less than 5 g/dL, who decline blood transfusion, die without the use of extreme measures such as hypotensive anesthesia, hypothermia, muscle paralysis and sedation. (29) However, despite the need for a non-blood therapy to treat massive hemorrhage, the use of a substitute for blood, such as an oxygen carrying polymerized hemoglobin solution, has not been addressed for such treatment.
What is needed is an alternative oxygen-carrier that can be administered in large quantities and provide immediate life-sustaining therapy until adequate red blood cell hemoglobin levels (RBC hemoglobin concentration) can be restored.